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A phase 2 study of intravenous panobinostat in patients with castration-resistant prostate cancer

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Abstract

Purpose

Panobinostat, a pan-deacetylase inhibitor, increases acetylation of proteins associated with growth and survival of malignant cells. This phase 2 study evaluated the efficacy of intravenous (IV) panobinostat in patients with castration-resistant prostate cancer (CRPC) who had previously received chemotherapy. The primary end point was 24-week progression-free survival. Secondary end points included safety, tolerability, and the proportion of patients with a prostate-specific antigen (PSA) decline.

Methods

IV panobinostat (20 mg/m2) was administered to patients on days 1 and 8 of a 21-day cycle. Tumor response was assessed by imaging every 12 weeks (4 cycles) according to modified response evaluation criteria in solid tumors (Scher et al. in Clin Cancer Res 11:5223–5232, 23), and PSA response was defined as a 50 % decrease from baseline maintained for ≥4 weeks. Safety monitoring was routinely performed and included electrocardiogram monitoring.

Results

Of 35 enrolled patients, four (11.4 %) were alive without progression of disease at 24 weeks. PSA was evaluated in 34 (97.1 %) patients: five (14.3 %) patients demonstrated a decrease in PSA but none ≥50 %; one patient (2.9 %) had carcinoembryonic antigen as a marker of his prostate cancer, which declined by 43 %. Toxicities regardless of relationship to panobinostat included fatigue (62.9 %), thrombocytopenia (45.7 %), nausea (51.4 %), and decreased appetite (37.1 %).

Conclusions

Despite promising preclinical data and scientific rationale, treatment with IV panobinostat did not show a sufficient level of clinical activity to pursue further investigation as a single agent in CRPC.

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Acknowledgments

This study was funded by Novartis Pharmaceuticals Corporation. Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals Corporation. We thank Kerry K. Brinkman, PhD, for medical editorial assistance with this manuscript.

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Authors and Affiliations

  1. Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Dana E. Rathkopf & Howard I. Scher

  2. Siteman Cancer Center, Barnes-Jewish Hospital, Washington University School of Medicine, St. Louis, MO, USA

    Joel Picus

  3. Greenebaum Cancer Center, University of Maryland, Baltimore, MD, USA

    Arif Hussain

  4. British Columbia Cancer Agency, Kelowna, BC, Canada

    Susan Ellard

  5. British Columbia Cancer Agency, Vancouver, BC, Canada

    Kim Nguyen Chi

  6. Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA

    Thomas Nydam, Erin Allen-Freda & Kaushal Kishor Mishra

  7. Novartis Pharma AG, Basel, Switzerland

    Maria Grazia Porro

  8. Paul P. Carbone Cancer Center, University of Wisconsin, Madison, WI, USA

    George Wilding

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  1. Dana E. Rathkopf
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  10. Howard I. Scher
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Correspondence to Dana E. Rathkopf.

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Rathkopf, D.E., Picus, J., Hussain, A. et al. A phase 2 study of intravenous panobinostat in patients with castration-resistant prostate cancer. Cancer Chemother Pharmacol 72, 537–544 (2013). https://doi.org/10.1007/s00280-013-2224-8

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  • DOI: https://doi.org/10.1007/s00280-013-2224-8

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